The primary goals of this K24 competing renewal application are to enable Roger Weiss, M.D., to 1) continue to conduct and extend his patient-oriented research (POR) with drug dependent patients, particularly those with co-occurring disorders; and 2) provide intensive and high-quality mentorship to early-career investigators in POR. A K24 renewal will continue to give Dr. Weiss protected time for research and mentoring that would otherwise be spent on clinical and administrative duties. Dr. Weiss, Professor of Psychiatry at Harvard Medical School and Chief of the Division of Alcohol and Drug Abuse at McLean Hospital, Belmont, Massachusetts, has conducted POR since 1980, emphasizing studies that 1) integrate different treatment approaches, and 2) influence clinical practice. Since receiving a K24 award in September 2007, Dr. Weiss has accomplished the major goals of his original application. He has mentored 35 junior investigators, including 17 with K awards. He has authored 72 publications, including 34 publications with a mentee as first author. He successfully completed a randomized controlled trial of a community-friendly version of Integrated Group Therapy that he developed for patients with bipolar disorder and substance dependence, and successfully led a multi-site study of prescription opioid dependence treatment in the NIDA Clinical Trials Network (CTN). Dr. Weiss' research plan for this renewal application includes continued work as a Node PI in the NIDA CTN, in which he is leading a long-term follow-up study of patients with prescription opioid dependence. He will also serve as Co-Investigator or consultant on several studies with mentees as PI. Further, he plans to submit proposals to 1) expand the scope of Integrated Group Therapy to include all mood disorders, and 2) study treatment approaches for pain clinic patients who misuse opioids. Dr. Weiss' mentoring plan includes training his mentees in 1) clinical aspects of drug abuse; 2) designing and implementing drug abuse research studies; 3) preparing scientific papers and presentations; 4) writing successful grant applications; and 5) responsible conduct of research. He will accomplish this with a combination of individual and group meetings; collaborative mentoring; role modeling; and integrating mentoring with the Harvard Clinical and Translational Science Award (CTSA) Consortium. Dr. Weiss' career development plan involves learning more about treatment and clinical research with patients with severe pain and opioid dependence in a pain clinic; longitudinal data analytic strategies; and genetics. These activities will simultaneously enhance Dr. Weiss' research and his mentoring skills. The public health importance of this application is related to the need to develop new and effective treatments for drug dependent and dually diagnosed patients, and the need to train the next generation of investigators to develop the skills they require to effectively conduct POR with this patient population.